US20220275059A1 - Antibodies - Google Patents
Antibodies Download PDFInfo
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- US20220275059A1 US20220275059A1 US17/432,745 US202017432745A US2022275059A1 US 20220275059 A1 US20220275059 A1 US 20220275059A1 US 202017432745 A US202017432745 A US 202017432745A US 2022275059 A1 US2022275059 A1 US 2022275059A1
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Definitions
- the invention relates to antibodies and antigen-binding fragments thereof that recognize the spike (S) protein of Middle East respiratory syndrome coronavirus (MERS-CoV).
- S spike protein of Middle East respiratory syndrome coronavirus
- Middle East respiratory syndrome is caused by the zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV).
- MERS-CoV Middle East respiratory syndrome coronavirus
- the virus infects camels and dromedaries and can be transferred to humans. Human-to-human transmission is inefficient, but can occur at close contact such as in households or hospital settings among patients and from patients to health-care workers. It is an airway infection with fever, coughing and shortness of breath as the primary symptoms. MERS can lead to serious pneumonia and kidney failure leading to death. MERS is associated with high mortality rates (according to the WHO, in 2015 approximately 36% of reported patients with MERS died; see WHO MERS-CoV Global Summary and Assessment of Risk, August 2018 (WHO/MERS/RA/August18)).
- the invention provides an antibody that binds to Middle East Respiratory Syndrome coronavirus (MERS-CoV) spike protein (MERS-S).
- MERS-CoV Middle East Respiratory Syndrome coronavirus
- the antibody is capable of inhibiting the infection of human cells by MERS-CoV.
- the antibody binds to the S2 domain of MERS-S. In some embodiments, the antibody binds to the S2 domain of MERS-S and is cross-reactive for one or more other human coronaviruses, such as Severe Acute Respiratory Syndrome coronavirus (SARS-CoV),
- SARS-CoV Severe Acute Respiratory Syndrome coronavirus
- HKU1 HKU1, 0C43 and/or murine hepatitis virus (MHV).
- the antibody binds to the Si domain of MERS-S. In some embodiments, the antibody binds to the Si domain of MERS-S and inhibits the sialic acid-binding activity of MERS-S.
- the invention further provides a combination of antibodies comprising: (i) a antibody that binds to the S2 domain of MERS-S and (ii) a antibody that binds to the S1 domain of MERS-S.
- the antibody that binds to the S2 domain of MERS-S and the antibody that binds to the S1 domain of MERS-S are human antibodies.
- the invention further provides a combination of antibodies comprising: (i) an antibody that binds to the S2 domain of MERS-S and (ii) an antibody that binds to the S1 domain of MERS-S and inhibits the sialic acid-binding activity of MERS-S.
- the antibody that binds to the S2 domain of MERS-S and the antibody that binds to the S1 domain of MERS-S are human antibodies.
- the invention further provides an antibody that binds to MERS-S and cross-reacts with other Coronaviruses.
- the invention further provides an isolated nucleic acid encoding the antibody of the invention.
- the invention further provides a vector comprising the nucleic acid of the invention.
- the invention further provides a host cell comprising the vector of the invention.
- the invention further provides a pharmaceutical composition comprising the antibody of the invention, or the combination of antibodies of the invention, and a pharmaceutically acceptable carrier.
- the invention further provides an antibody of the invention, or a combination of antibodies of the invention, for use in therapy.
- the therapy is preventing, treating or ameliorating betacoronavirus infection, such as MERS-CoV infection.
- the invention further provides an antibody of the invention, or a combination of antibodies of the invention, for use in therapy of Coronaviruses other than MERS-CoV.
- FIG. 1 Generation and characterization of monoclonal H2L2 antibodies targeting the MERS-CoV spike protein.
- S1 subunit Structure of MERS spike protein.
- the S1 subunit (residues 1-751) is mainly responsible for mediating viral particle attachment to the cell surface and is dependent on the dipeptidyl peptidase 4 (DPP4) receptor (also known as CD26).
- DPP4 dipeptidyl peptidase 4
- the S1 subunit folds into four distinct domains designated S1 A to S1 D .
- S1 A has sialic acid binding activity, which may aid in virion attachment to host cells.
- S1 B is the receptor binding domain (RBD), and it is via this domain that MERS-CoV binds to the cell surface entry receptor DPP4.
- the S2 subunit functions in virus-host cell membrane fusion.
- Binding of the S1 subunit to the DPP4 receptor is thought to trigger conformational changes in the S2 subunit, which then inserts its fusion peptide into the target cell membrane to form a six-helix bundle fusion core that prepares the viral and cell membranes for fusion.
- C The MERS-CoV spike (S) protein and recombinant soluble MERS-CoV S antigens used for immunization of H2L2 transgenic mice to generate human monoclonal antibodies (mAbs).
- Upper panel Schematic representation of the MERS-CoV S protein, indicated are S subunits (S1 and S2), S1 domains (A through D), and known biological functions.
- Middle panel Schematic representation of recombinant soluble MERS-CoV S antigens, including the MERS-CoV S S1 subunit (MERS-S1), the ectodomain of its S2 subunit (MERS-S ecto ) or the entire MERS-S ectodomain)(MERS-S ecto ), the latter containing a mutation at the furin cleavage site at the S1/S2 junction and a C-terminally fused T4 foldon trimerization tag to increase trimer stability (T4). Positions of signal peptides (SP) and StrepTag-affinity tags (ST) are indicated.
- Lower panel Immunization schedule for H2L2 mice.
- mice To generate monoclonal antibodies (mAbs) targeting the MERS-CoV S protein, groups of H2L2 mice (six mice/group) were immunized with either MERS-S1 (6x), or sequentially immunized with MERS-S ecto ) (3x), MERS-S2 ecto (2x) and MERS-S ecto (1x).
- Booster immunizations were done with two-week intervals and B-cells were harvested from spleen and lymph nodes four days after the last immunization.
- the percentage of mAbs that was reactive to S1 but not to the S1 A , S1 B or S1 CD ) domains (S1 other ) is also shown.
- Virus neutralization by S1-reactive mAbs was analysed using the luciferase-encoding MERS-CoV S pseudotyped VSV particles.
- FIG. 2 Variable region sequences of anti-MERS-S1 H2L2 antibodies and distribution of epitope groups over multiple domains of the MERS-CoV spike protein.
- MERS-S specific mAbs bind MERS-S ecto with high affinity.
- the binding kinetics and affinity of anti-MERS-S mAbs and DPP4 receptor to recombinant soluble MERS-S ecto was measured by bio-layer interferometry (BLI).
- Antibodies and receptor were immobilized on the sensor surface, followed by injection of the MERS-S ecto at 200, 67, 22 and 7.4 nM concentrations (represented by the blue, red, green purple lines, respectively).
- the kinetics constants were calculated using 1:1 Langmuir binding model on Fortebio Data Analysis 7.0 software.
- FIG. 3 Binding and Cross-binding (A) Binding affinities of anti-MERS-S1 H2L2 antibodies. These affinities were determined via kinetic measurements obtained using a ForteBio Octet instrument.
- MERS-CoV S expressing cells S protein that was C-terminally extended with the green fluorescent protein, which was used for gating MERS-CoV S expressing cells.
- Cells were stained with eight anti-MERS-S mAbs and an anti-MERS-S control antibody with 5 ⁇ g/ml of each antibody.
- Antibody binding to cells was detected by flow cytometry using Alexa Fluor 649 conjugated goat anti-human IgG antibodies and mean fluorescence intensities (MFIs) were calculated.
- FIG. 4 Naturally occurring amino acid substitutions in receptor binding subdomain of MERS-S (amino acids 483-566 of MERS-S). GB acc. no refers to the Genbank accession no.
- DPP4-interacting residues are indicated with an asterisk.
- the boxed mutations are those that were selected to test for anti-MERS-S 1 antibody reactivity to MERS-S 1 variants.
- FIG. 5 The anti-MERS-S 1 antibodies display broad reactivity to Fc-tagged MERS-S 1 variants containing naturally occurring amino acid substitutions in the receptor binding subdomain. Residues L507 and D509 were found to be critical epitope residues for antibody 4.6e10 binding to MERS-S1. (B) Position of residues L507 and D509 on the surface of the receptor binding subdomain of MERS-S. The DPP4 receptor is shown as a ribbon diagram.
- FIG. 6 (A) Surface representation of the MHV S trimer coloured according to sequence conservation (left hand image). Surface representation of the MI-IV S trimer highlighting the peripheral position of the fusion peptide (middle image). Ribbon diagrams of the MI-IV S trimer showing the overlapping positions of the fusion peptide (residues 870-887, coloured ribbons) and of a major antigenic determinant identified for MHV and SARS-CoV (residues 875-905, coloured spheres) (right hand image). Exposed conserved epitopes form an attractive target for the development of neutralizing antibodies with broad reactivity. This figure originated from Walls et al. (2016) Nature 531(7592):114-117.
- FIG. 8 MERS-S2 reactivity.
- Antibodies 3.5g6 and 1.6c7 can neutralize MERS-S pseudotyped vesicular stomatitis virus (VSV).
- VSV vesicular stomatitis virus
- FIG. 9 Heavy and light chain variable region sequences of anti-MERS-S2 H2L2 antibodies. The CDR1, 2 and 3 regions are indicated on top. Below each of the germline VH and VK sequences is a group of neutralizing antibodies (neutralization was determined by DPP4-S1 blocking and MERS-S VSV pseudo-virus neutralization assays). Underlined amino acids are somatic hypermutations. 1.6c7 recognizes a linear epitope (conserved residues) in the MERS-CoV-S2 subunit and cross-reacts with other beta corona viruses.
- FIG. 10 Cross-reactivity of anti-MERS-S2 antibodies with other CoV S or S2 proteins by ELISA.
- Antibody 1.6c7 is reactive against MERS, MHV and SARS.
- Secto S ectodomain.
- FIG. 11 Antibody 1.6c7 neutralizes MERS-S and MHV-S VSV pseudoparticles. The neutralization capacity for antibody 1.6c7 against beta-coronaviruses is shown.
- FIG. 12 Anti-MERS-S2 antibodies recognize linear (L) and conformational (C) epitopes. ELISA of anti-MERS-S2 antibodies with MERS-S eco domain antigen at denaturing (d) and non-denaturing (d) conditions identifying C or L epitopes.
- FIG. 13 Epitope mapping of anti-MERS-S2 antibodies recognizing linear epitopes by ELISA using overlapping MERS-S2 peptides.
- FIG. 14 The epitope of 1.6c7 was determined to be a linear epitope (residues 1230-1242 of the S protein, namely DFQDELDEFFKNV (SEQ ID NO: 82)). Epitope mapping was performed by ELISA-based Pepscan analysis using overlapping peptides corresponding to a conserved region of the MERS-S2 ectodomain. In addition alanine scanning of the 15 amino acid linear epitope of 1.6c7 was performed. This epitope mapped to a conserved CoV domain (see dashed box). The mAb showed broader reactivity to MHV and SARS-CoV S in ELISA.
- FIG. 15 The epitope of 2.6h11 in MERS-S2 is not conserved among betacoronavirus S proteins.
- FIG. 16 Functional properties of anti-MERS S protein H2L2 antibodies.
- Anti-MERS-CTRL H1H15211P is an IgG1 described in WO2015179535.
- FIG. 17 Heavy variable region sequences of anti-MERS-S 1 HCAb antibodies. Germline VH sequences are at the top of each group of sequences (labelled as 3-33, 3-74 and 3-23). The CDR1, 2 and 3 regions are indicated using labels at the top of the figure. Below each of the germline VH sequences is a group of neutralizing antibodies (neutralization was determined by MERS-S VSV pseudo-virus neutralization assays). Underlined amino acids are somatic hypermutations.
- FIG. 18 SDS-PAGE analysis of purified monoclonal antibodies. Two microgram of the eight lead anti-MERS-S mAbs, an anti-MERS control antibody and an isotype control antibody were analysed by SDS-PAGE. All antibodies, were expressed in human HEK-293T cells as human IgG1 isotype and purified using Protein A affinity purification.
- FIG. 19 Virus neutralization and receptor binding inhibition by anti-MERS-S mAbs.
- A Analysis of MERS-CoV neutralizing activity by anti-MERS-S mAbs using MERS-S pseudotyped, luciferase-encoding VSV .
- a previously described RBD-specific, MERS-CoV-neutralizing human monoclonal antibody (anti-MERS-CTRL) and irrelevant isotype monoclonal antibody (Iso-CTRL) were included as positive and negative control, respectively.
- Luciferase-expressing VSV particles pseudotyped with the MERS-CoV S protein were incubated with antibodies at the indicated concentrations and the mix was used to transduce Vero cells.
- FIG. 20 Neutralization of anti-MERS S1 B mAbs correlates with receptor binding inhibition.
- A Receptor binding inhibition by anti-MERS-S mAbs, determined by an ELISA-based assay. Recombinant soluble MERS-S ecto was preincubated with serially diluted anti-MERS-CoV mAbs and added to ELISA plates coated with soluble DPP4. Binding of MERS-S ecto t o DPP4 was measured using HRP-conjugated antibody recognizing the Streptag affinity tag on MERS-S ecto . Data represent the mean ( ⁇ standard deviation, SD) of three independent experiments.
- B Table showing the concentration of mAb that gives half maximal receptor binding inhibition (RBI 50 ).
- FIG. 21 Anti-MERS S1 A and S2 mAbs block with MERS-CoV domain specific functions.
- the anti-MERS-S ecto mAb 1.10f3 interferes with MERS-S1 A -mediated sialic acid binding, determined by a hemagglutination inhibition assay (Li, Hulswit et al. 2017).
- the sialic-acid binding domain S1 A of MERS-S was fused to lumazine synthase (LS) protein that can self-assemble to form 60-meric nanoparticle (S1 A -LS), which enables multivalent, high affinity binding of the MERS-S1 A domain to sialic acid on erythrocytes.
- LS lumazine synthase
- the anti-MERS-52 mAbs 1.6c7 and 3.5g6 block MERS-S-mediated cell-cell fusion.
- Huh-7 cells were transfected with plasmid expressing MERS-CoV S, C-terminally fused to GFP. Two days after transfection, cells were treated with trypsin to activate membrane fusion function of the MERS-CoV S protein, and incubated in the presence or absence of anti-MERS-S2 mAbs 1.6c7 and 3.5g6, or the anti-MERS-S1 B mAb 7.7g6 and anti-MERS-S1 A 1.10f3, all at 10 ⁇ g/ml. Formation of MERS-S mediated cell-cell fusion was visualized by fluorescence microscopy. Merged images of MERS-S-GFP expressing cells (green) and DAPI-stained cell nuclei (blue) are shown. Experiment was repeated two times and representative images are shown.
- FIG. 22 The 1.10f3 antibody, which targets S1 A domain blocks binding of MERS-S1 A to sialic acid as shown by MERS-SlA haemagglutination inhibition assay.
- FIG. 23 Animal experiment protocol. The experiment was performed in hDPP4-transgenic mice to test prophylactic activity of eight human anti-MERS-S monoclonal antibodies.
- FIG. 24 Human anti-MERS-S mAbs protect mice against lethal MERS-CoV challenge: survival rates. Fifty microgram of antibody (equivalent to 1.8 mg mAb/kg body weight) was infused intraperitoneally in K18-hDPP4-transgenic mice 6 hours before challenge with TCID50 of MERS-CoV. Five mice per group were used in the experiment. Survival rates were monitored daily until 12 days post-inoculation.
- FIG. 25 Human anti-MERS-S mAbs protect mice against lethal MERS-CoV challenge: weight loss. Weight loss was monitored (expressed as a percentage of the initial weight) was monitored daily until 12 days post-inoculation in the experiment described in the legend for FIG. 24 above.
- FIG. 26 SDS-PAGE analysis of purified, recombinant MERS-CoV S antigens. SDS-PAGE analysis of purified MERS-CoV S antigens (2 microgram each) used for immunization of H2L2 transgenic mice (A) or for ELISA-based screening of antibodies (B).
- FIG. 27 Characterization of anti-MERS-S1 H2L2 antibodies from antibody-containing hybridoma supernatants.
- antibody-containing hybridoma supernatants selected based on an initial MERS-S1 ELISA screen
- S1 A , S1 B or S1 CD individual domains of S1
- S1 CD individual domains of S1
- FIG. 28 Binding competition of anti-MERS-S mAbs using bio-layer interferometry. Immobilized MERS-S ecto antigen was saturated in binding with a given anti-MERS-S H2L2 mAb (step 1) and then exposed to binding by a second H2L2 mAb (step 2). Additional binding of the second antibody indicates the presence of an unoccupied epitope, whereas lack of binding indicates epitope blocking by the first antibody. As a control, the first mAb was also included in the second step to check for self-competition.
- FIG. 29 H 2 L2 antibodies were purified from hybridoma supernatants that exhibited neutralizing activity. Neutralizing activity of purified H2L2 antibodies was assessed using MERS-S pseudotyped VSV and half-maximal inhibitory concentrations (IC 50 ; ⁇ g/ml) are shown.
- H2L2 antibodies were purified from hybridoma supernatants with neutralizing activity that were reactive to MERS-S1 B .
- H2L2 antibodies were purified from hybridoma supernatants showing MERS-S2 and MERS-S1 A domain reactivity.
- Selection of lead mAbs was based on their potency to neutralize MERS-CoV relative to other mAbs within an epitope group (epitope groups are marked by shaded blocks), and on their unique VH and VL region sequences. Eight monoclonal antibodies (shown by red arrows) with epitopes distributed throughout different domains of the MERS-CoV spike protein were selected as lead antibodies for further detailed biophysical and functional characterization.
- FIG. 30 Binding of anti-MERS-S mAbs to cell surface expressed MERS-CoV spike protein.
- Huh-7 cells were transfected with plasmid expressing a full-length MERS-CoV S construct.
- the encoding MERS-CoV S protein was C-terminally extended with the green fluorescent protein (GFP) and contained a mutated furin cleavage site to prevent cell-cell fusion.
- GFP green fluorescent protein
- Fixed, nonpermeabilized MERS-CoV S transfected cells were stained with the eight lead anti-MERS-S mAbs, an anti-MERS control antibody and an isotype control antibody with 1.25 ⁇ g/ml of each antibody.
- Antibody binding to cells was detected by fluorescence microscopy using Alexa Fluor 568 conjugated goat anti-human IgG antibodies (red channel). MERS-S-GFP transfected cells were detected by GFP fluorescence (green channel).DAPI was used for nuclear staining (blue channel). Panels on the right represent overlay profiles of the red, green and blue channels.
- FIG. 31 Neutralization activity of anti-MERS-S HCAbs. Analysis of MERS-CoV neutralizing activity by anti-MERS-S HCAbs using MERS-S pseudotyped, luciferase-encoding VSV. At 24 h post-infection luciferase expression was measured and neutralization (%) was calculated as the ratio of luciferase signal relative to luciferase readout in the absence of mAb. The experiment was performed twice and 50% inhibition titers (ug/ml) for each experiment are shown.
- FIG. 32 Anti-MERS-S1 HCAb variable domain sequences. Boxed residues contribute to CDR3 in each antibody sequence.
- FIG. 33 Epitope binning anti-MERS HCAb.
- MERS-S1-Fc was loaded on huFc capture tips
- H2L2 antibodies were used at 10micrograms/m1 and HCAbs at 20micrograms/ml.
- 1H5 HCAb competes with 1.3g2 H2L2 for epitope binding. 1H5 HCAb binds to a different epitope from that bound by the 1.8e5 H2L2 (7.5d3 H2L2) group. 1H5 HCAb interferes with the binding of 4.6e10 H2L2.
- 1G3 HCAb does not interfere with the binding of 1.2g5 H2L2 (group 1.3g2 H2L2) or 4.6e10 H2L2. 1G3 HCAb does not interfere with the binding of 1.8e10 H2L2 (7.5d3). However, once 1.8e10 H2L2 (7.5d3) is bound, it abolishes the binding of 1G3 HCAb almost completely.
- FIG. 34 Table showing virus neutralization and receptor binding inhibition by anti-MERS-S mAbs.
- the examples show that the 1.6c7 antibody binds to the S2 domain (see FIGS. 8 and 10 ).
- the examples also show that the 1.6c7 antibody binds to MERS-S with a strong binding affinity ( FIG. 3A shows an affinity value of approximately 5.0 ⁇ 10 ⁇ 10 M).
- This antibody is also shown to be capable of neutralizing MERS-S VSV pseudoparticles infection (see FIGS. 8, 16, 19 and 20 ).
- the 1.6c7 antibody is advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC50 of approximately 0.59 ⁇ g/ml (see FIG. 16 ).
- the examples also show that a human IgG1 comprising the heavy and light chain variable sequences of the 1.6c7 antibody is advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC 50 of approximately 2.5 ⁇ g/ml (see FIG. 16 ).
- the inventors believe that the 1.6c7 antibody may neutralize MERS-CoV infection by inhibiting membrane fusion (see FIG. 21 ).
- the examples also show that the 1.6c7 antibody is protective in vivo in that 100% of treated mice survived after 12 days post-infection with MERS-CoV (see FIG. 24 ).
- the 1.6c7 antibody is also cross-reactive for SARS, MI-IV and NL63 coronaviruses (see FIG. 10 ).
- the antibody is useful for preventing, treating and diagnosing several types of betacoronavirus.
- the reason for this cross-reactivity is thought to be that the linear epitope recognized by the 1.6c7 antibody, residues 1230-1242 of the MERS-S protein (DFQDELDEFFKNV), that is highly conserved across coronavirus species (see FIGS. 12, 13, 14 and 16 ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74. Accordingly, in some embodiments, the anti-MERS-S antibody binds to an epitope that comprises residues 1230-1242 of the MERS-S protein (SEQ ID NO: 81).
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74.
- the examples show that the 3.5g6 antibody binds to a conformational epitope in the S2 domain (see FIGS. 8, 10 and 12 ).
- the examples also show that the 3.5g6 antibody binds to MERS-S with a strong binding affinity ( FIG. 3A shows an affinity value of approximately 2.2 ⁇ 10 ⁇ 9 M).
- This antibody is also shown to be capable of neutralizing MERS-S VSV pseudoparticles infection (see FIGS. 8, 16 and 19 ).
- the inventors believe that the 3.5g6 antibody may neutralize MERS-CoV infection by inhibiting membrane fusion (see FIG. 21 ).
- the examples also show that the 3.5g6 antibody is protective in vivo in that 100% of treated mice survived after 12 days post-infection with MERS-CoV (see FIG. 24 ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the 7.7g6, 1.6f9, 1.2g5, 5.2b7, 5.5e11 and 1.3g2 antibodies bind to the same epitope group in the S1 B domain (see FIGS. 5A , 16 and 19).
- the examples show that each of the 7.7g6, 1.6f9, 1.2g5, 5.2b7, 5.5e11 and 1.3g2 bind to MERS-S1 with a strong binding affinity ( FIG. 3A shows affinity values of approximately 3.6 ⁇ 10 ⁇ 10 , 5.3 ⁇ 10 ⁇ 10 , 8.1 ⁇ 10 ⁇ 11 , 3.6 ⁇ 10 ⁇ 10 , 3.0 ⁇ 10 ⁇ 10 and 1.1 ⁇ 10 ⁇ 9 , respectively).
- Each of the 7.7g6, 1.6f9, 1.2g5, 5.2b7 and 5.5e11 antibodies is also shown to be capable of neutralizing MERS-S VSV pseudoparticles infection (see FIGS. 16 and 19 ).
- the 7.7g6, 1.6f9, 1.2g5, 5.2b7 and 5.5e11 antibodies are advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC50 of approximately 0.00011, 0.00038, 0.00062, 0.00081 and 0.0017 ⁇ g/ml, respectively (see FIG. 16 ).
- the 7.7g6, 1.6f9, 1.2g5, 5.2b7 and 5.5e11 antibodies are advantageously capable of neutralizing MERS-CoV infectivity with an IC50 of approximately 0.0003, 0.003, 0.001, 0.005 and 0.0006 ⁇ g/ml, respectively (see FIG. 16 ).
- the examples also show that a human IgG1 comprising the heavy and light chain variable sequences of one of the 7.7g6, 1.6f9 and 1.2g5 antibodies is advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC50 of approximately 0.02, 0.019 and 0.007 ⁇ g/ml, respectively (see FIG. 16 ).
- the 7.7g6, 1.6f9 and 1.2g5 antibodies are also shown to be capable of inhibiting MERS-S-DPP4 receptor binding (see
- FIG. 20 The examples also show that each of the 7.7g6, 1.6f9 and 1.2g5 antibodies is protective in vivo in that 80% (1.619) or 100% (7.7g6, 1.2g5) of treated mice survived after 12 days post-infection with MERS-CoV (see FIG. 24 ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region of the amino acid sequence of SEQ ID NO: 49.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 20 and a light chain variable region of the amino acid sequence of SEQ ID NO: 40.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59.
- the 1.8e5 and 4.6e10 antibodies bind to the S1 B domain (see FIGS. 5A, 16 and 19 ).
- the examples show that each of the 1.8e5 and 4.6e10 antibodies binds to MERS-S1 with a strong binding affinity ( FIG. 2F and 3A shows affinity values of approximately 3.2 ⁇ 10 ⁇ 10 and 3.6 ⁇ 10 ⁇ 10 , respectively).
- Each of the 1.8e5 and 4.6e10 antibodies is also shown to be capable of neutralizing MERS-S VSV pseudoparticles infection (see FIGS. 16 and 19 ).
- the 1.8e5 and 4.6e10 antibodies are advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC50 of approximately 0.09026 and 0.03131 ⁇ g/ml, respectively (see FIG. 16 ).
- the 1.8e5 and 4.6e10 antibodies are advantageously capable of neutralizing MERS-CoV infectivity with an IC50 of approximately 1.25 and 0.32 ⁇ g/ml, respectively (see FIG. 16 ).
- the examples also show that a human IgG1 comprising the heavy and light chain variable sequences of one of the 1.8e5 and 4.6e10 antibodies is advantageously capable of neutralizing MERS-S pseudovirus infectivity with an IC50 of approximately 2.59 and 0.07 ⁇ g/ml, respectively (see FIG. 16 ).
- the 1.8e5 and 4.6e10 antibodies are also shown to be capable of inhibiting MERS-S-DPP4 receptor binding (see FIG. 20 ).
- the examples also show that each of the 1.8e5 and 4.6e10 antibodies is protective in vivo in that 80% of treated mice survived after 12 days post-infection with MERS-CoV (see FIG. 24 ).
- the epitope recognized by the 4.6e10 antibody is shown to comprise residues 507 and 509 of the MERS-S protein (see FIG. 5A ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67. Accordingly, in some embodiments, the anti-MERS-S antibody binds to an epitope that comprises residues 507 and 509 of the MERS-S protein (SEQ ID NO: 81).
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67.
- the 1.10f3 antibody targets the sialic acid binding MERS S1 A domain (see FIG. 5A ) and inhibits Sia-binding activity (e.g. as determined by a haemagglutination inhibition assay in FIG. 22 ).
- the examples show that the 1.10f3 antibody binds to MERS-S1 with a strong binding affinity ( FIG. 3A shows an affinity value of approximately 4.8 ⁇ 10 ⁇ 9 M).
- the examples also show that the 1.10f3 antibody is protective in vivo in that 40% of treated mice survived after 12 days post-infection with MERS-CoV (see FIG. 24 ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.
- the 1.8c5 and 7.1c12 antibodies bind to the S1 B domain (see FIGS. 5A and 29 (A)). Each of these antibodies belongs to the 1.8e5 group.
- the 1.8c5 antibody exhibits neutralising activity (see FIG. 29(A) ). Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the 1.8c5 and/or 7.1c12 antibodies.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2993.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 299 and a light chain variable region of the amino acid sequence of SEQ ID NO: 300.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 307 and a light chain variable region of the amino acid sequence of SEQ ID NO: 308.
- the 7.7a9 antibody binds to the S1 B domain and exhibits neutralising activity (see FIGS. 5(A) and 29(A) ).
- This antibody belongs to the 4.6e10 group. Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the 7.7a9 antibody.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 315 and a light chain variable region of the amino acid sequence of SEQ ID NO: 316.
- 3A shows affinity values of approximately 1.2 ⁇ 10 ⁇ 10 , 1.2 ⁇ 10 ⁇ 10 , 1.3 ⁇ 10 ⁇ 10 , 1.3 ⁇ 10 ⁇ 10 , 5.4 ⁇ 10 ⁇ 10 , 4.3 ⁇ 10 ⁇ 10 , 4.0 ⁇ 10 ⁇ 10 , 1.1 ⁇ 10 ⁇ 10 , 2.1 ⁇ 10 ⁇ 10 , 3.5 ⁇ 10 ⁇ 10 , 1.2 ⁇ 10 ⁇ 8 , 2.6 ⁇ 10 ⁇ 9 , 1.9 ⁇ 10 ⁇ 9 , 6.0 ⁇ 10 ⁇ 9 , 2.0 ⁇ 10 ⁇ 10 , 3.6 ⁇ 10 ⁇ 10 , 1.1 ⁇ 10 ⁇ 10 , 8.6 ⁇ 10 ⁇ 10 , 6.8 ⁇ 10 ⁇ 10 and 4.4 ⁇ 10 ⁇ 10 , respectively).
- the 1.3h2 antibody is shown to specifically bind to the S1 B domain (see FIG. 5A ).
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2 and a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2 and a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2 and a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2 and a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 2 and a light chain variable region of the amino acid sequence of SEQ ID NO: 42.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 3 and a light chain variable region of the amino acid sequence of SEQ ID NO: 43.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 4 and a light chain variable region of the amino acid sequence of SEQ ID NO: 44.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 5 and a light chain variable region of the amino acid sequence of SEQ ID NO: 45.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 6 and a light chain variable region of the amino acid sequence of SEQ ID NO: 46.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and a light chain variable region of the amino acid sequence of SEQ ID NO: 47.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region of the amino acid sequence of SEQ ID NO: 48.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region of the amino acid sequence of SEQ ID NO: 50.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region of the amino acid sequence of SEQ ID NO: 51.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 12 and a light chain variable region of the amino acid sequence of SEQ ID NO: 52.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 13 and a light chain variable region of the amino acid sequence of SEQ ID NO: 34.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 14 and a light chain variable region of the amino acid sequence of SEQ ID NO: 35.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 15 and a light chain variable region of the amino acid sequence of SEQ ID NO: 53.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 16 and a light chain variable region of the amino acid sequence of SEQ ID NO: 61.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 21 and a light chain variable region of the amino acid sequence of SEQ ID NO: 36.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 23 and a light chain variable region of the amino acid sequence of SEQ ID NO: 54.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 24 and a light chain variable region of the amino acid sequence of SEQ ID NO: 37.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 25 and a light chain variable region of the amino acid sequence of SEQ ID NO: 64.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 27 and a light chain variable region of the amino acid sequence of SEQ ID NO: 38.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 30 and a light chain variable region of the amino acid sequence of SEQ ID NO: 55.
- the 4.2f1 and 4.9e5 antibodies bind to the S1 B domain and exhibit neutralising activity (see FIG. 29(A) ). Each of these antibodies belongs to group 1.3g2. Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the 4.2f1 and/or 4.9e5 antibodies.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 283 and a light chain variable region of the amino acid sequence of SEQ ID NO: 284.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 291 and a light chain variable region of the amino acid sequence of SEQ ID NO: 292.
- the 7.4f3 antibody binds to the S1 B domain (see FIG. 5A ). Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the 7.4f3 antibody.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 323 and a light chain variable region of the amino acid sequence of SEQ ID NO: 324.
- the 7.8h1 antibody binds to the S1 domain (see FIG. 29A ). Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the 7.8h1 antibody.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 331 and a light chain variable region of the amino acid sequence of SEQ ID NO: 332.
- the 1.6a9, 2.6h11, 1.17f10, 1.12g2, 1.5d6 and 1.13a9 antibodies bind to the S2 domain (see FIG. 29A ). These antibodies do not exhibit neutralising activity in the assays tested (see FIGS. 8 and 29A ). Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with one or more of the 1.6a9, 2.6h11, 1.17f10, 1.12g2, 1.5d6 and 1.13a9 antibodies.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 339 and a light chain variable region of the amino acid sequence of SEQ ID NO: 340.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 347 and a light chain variable region of the amino acid sequence of SEQ ID NO: 348.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 355 and a light chain variable region of the amino acid sequence of SEQ ID NO: 356.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 363 and a light chain variable region of the amino acid sequence of SEQ ID NO: 364.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 371 and a light chain variable region of the amino acid sequence of SEQ ID NO: 372.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 379 and a light chain variable region of the amino acid sequence of SEQ ID NO: 380.
- the antibody binds to MERS-S with a KD of 10 ⁇ 7 M or less, 10 ⁇ 8 M or less, 10 ⁇ 9 M or less, or 10 ⁇ 10 M or less.
- antibody binding affinity is determined using an Octet® RED96 system (ForteBio, Inc.).
- a Flag-tagged S1 domain or a Flag-tagged S2 domain may be immobilized to an anti-Flag biosensor and incubated with varying concentrations of the antibody in solution, binding data are then collected.
- antibody binding affinity is determined by surface plasmon resonance.
- the antibody is capable of inhibiting the interaction between MERS-S and the DPP4 receptor by at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99% or 100%.
- the capability for inhibiting the interaction between MERS-S and the DPP4 receptor is measured in a blocking ELISA assay.
- the antibody is capable of neutralizing MERS-CoV infectivity of human host cells by more than 50%, by more than 60%, by more than 70%, by more than 80%, by more than 90%, by more than 95%, by more than 99% or by 100%.
- the 50% inhibitory concentration (IC50) value of the antibody for neutralizing MERS-CoV infectivity is less than 100 ⁇ g/ml, less than 50 ⁇ g/ml, less than 40 ⁇ g/ml, less than 30 ⁇ g/ml, less than 20 ⁇ g/ml, less than 15 ⁇ g/ml, less than 10 ⁇ g/ml, less than 5 ⁇ g/ml, less than 1 ⁇ g/ml, less than 0.1 ⁇ g/ml, less than 0.01 ⁇ g/ml, less than 0.001 ⁇ g/ml or less than 0.0001 ⁇ g/ml.
- the neutralizing capability of anti-MERS-S antibodies is measured in a virus-like particle (VLP) neutralization assay (Tang et al. (2012) PNAS 111(19):E2018-E2026).
- VLP virus-like particle
- the antibody is capable of interfering with the attachment of MERS-CoV S protein to sialic acid.
- the S1 A domain is thought to be responsible for binding of the S protein to sialic acid. Accordingly, antibodies that bind to the S1 A domain may be capable of interfering with the attachment of MERS-CoV S protein to sialic acid.
- this interference is assessed by determining the level of sialic-acid dependent hemagglutination by the MERS-S1 A domain (e.g. as described in Li, Hulswit et al. 2017). Inhibition of S1 A domain-mediated hemaglutination in this assay indicates that the test antibody is capable of interfering with the attachment of MERS-CoV S protein to sialic acid.
- the antibody is capable of interfering with interfering with MERS-CoV S protein-mediated membrane fusion.
- the S2 domain is thought to be responsible for mediating membrane fusion.
- antibodies that bind to the S2 domain may be capable of interfering with interfering with MERS-CoV S protein-mediated membrane fusion.
- a MERS-CoV-S driven cell-cell fusion assay may be used (e.g. an assay which uses a GFP-tagged MERS-CoV spike protein that has a mutated the furin cleavage site at the S 1/S2 junction). Inhibition of the formation of syncytia in this assay indicates that the test antibody is capable of interfering with MERS-CoV S protein-mediated membrane fusion.
- whether a test antibody competes with a reference antibody for binding to MERS-S is determined using an in vitro binding competition assay.
- a Flag-tagged S1 domain or a Flag-tagged S2 domain may be immobilized to an anti-Flag biosensor, the association of the reference antibody to the immobilized Flag-tagged S1 or S2 domain is then measured (e.g. using the Octet® RED96 system, ForteBio, Inc.) and then the degree of additional binding is assessed by exposing the immobilized Flag-tagged S1 or S2 domain to the test antibody in the presence of the reference antibody.
- the anti-MERS antibody recognizes MERS-CoV and one or more additional beta coronaviruses.
- the anti-MERS antibody recognizes: (i) MERS-CoV and mouse hepatitis virus (MHV), (ii) MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV), or (iii) MERS-CoV, MHV and SARS-CoV.
- the anti-MERS antibody is a heavy chain-only antibody.
- the examples show that the 1G3 heavy chain-only antibody binds to the Si domain with a strong binding affinity of approximately 2.17 ⁇ 10 ⁇ 8 .
- the 1G3 antibody is advantageously capable of neutralizing MERS-S pseudovirus infectivity (e.g. see FIG. 31 ). Similar functional properties can be expected to be associated with the heavy chain-only antibodies defined below which share structural and functional characteristics with the 1G3 heavy chain-only antibody.
- the invention further provides an anti-MERS-S heavy chain-only antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the invention further provides an anti-MERS-S heavy chain-only antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the heavy chain-only antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 75.
- the examples show that the 1H5 heavy chain-only antibody binds to the S1 domain with a strong binding affinity of approximately 1.09 ⁇ 10 ⁇ 8 .
- the 1H5 antibody is advantageously capable of neutralizing MERS-S pseudovirus infectivity (e.g. see FIG. 31 ). Similar functional properties can be expected to be associated with the heavy chain-only antibodies defined below which share structural and functional characteristics with the 1H5 heavy chain-only antibody.
- the invention further provides an anti-MERS-S heavy chain-only antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 78.
- the invention further provides an anti-MERS-S heavy chain-only antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 78.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the heavy chain-only antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 78.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 78.
- the examples show that the 1E10 heavy chain-only antibody binds to the S1 domain with a strong binding affinity of approximately 1 ⁇ 10 ⁇ 9 .
- the 1E10 antibody is advantageously capable of neutralizing MERS-S pseudovirus infectivity (e.g. see FIG. 31 ). Similar functional properties can be expected to be associated with the heavy chain-only antibodies defined below which share structural and functional characteristics with the 1E10 heavy chain-only antibody.
- the invention further provides an anti-MERS-S heavy chain-only antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 80.
- the invention further provides an anti-MERS-S heavy chain-only antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 80.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 80.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 80.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 80.
- the examples show that the 5F1 heavy chain-only antibody binds to the S1 domain and has MERS-CoV neutralising activity (see FIG. 31 ). Similar functional properties can be expected to be associated with the heavy chain-only antibodies defined below which share structural and functional characteristics with the 5F1 heavy chain-only antibody.
- the invention further provides an anti-MERS-S heavy chain-only antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the invention further provides an anti-MERS-S heavy chain-only antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the heavy chain-only antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 77.
- the invention further provides an anti-MERS-S heavy chain-only antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of any one of SEQ ID NOs: 410-420, 422-429 and 431-434.
- the invention further provides an anti-MERS-S heavy chain-only antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of any one of SEQ ID NOs: 410-420, 422-429 and 431-434.
- the invention further provides a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of any one of SEQ ID NOs: 410-420, 422-429 and 431-434.
- the invention further provides a heavy antibody comprising an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of any one of SEQ ID NOs: 410-420, 422-429 and 431-434.
- the invention further provides an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) of heavy chain variable region of the amino acid sequence of any one of SEQ ID NOs: 410-420, 422-429 and 431-434.
- CDRs complementarity determining regions
- the heavy chain-only antibody binds to MERS-S with a KD of 10 ⁇ 7 M or less, 10 ⁇ 8 M or less, 10 ⁇ 9 M or less, or 10 ⁇ 10 M or less.
- antibody binding affinity is determined using an Octet® RED96 system (ForteBio, Inc.).
- a Flag-tagged S1 domain or a Flag-tagged S2 domain may be immobilized to an anti-Flag biosensor and incubated with varying concentrations of the antibody in solution, binding data are then collected.
- antibody binding affinity is determined by surface plasmon resonance.
- the heavy chain-only antibody is capable of inhibiting the interaction between MERS-S and the DPP4 receptor by at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99% or 100%.
- the capability for inhibiting the interaction between MERS-S and the DPP4 receptor is measured in a blocking ELISA assay.
- the heavy chain-only antibody is capable of neutralizing MERS-CoV infectivity of human host cells by more than 50%, by more than 60%, by more than 70%, by more than 80%, by more than 90%, by more than 95%, by more than 99% or by 100%.
- the 50% inhibitory concentration (IC 50 ) value of the antibody for neutralizing MERS-CoV infectivity is less than 100 ⁇ g/ml, less than 50 ⁇ g/ml, less than 40 ⁇ g/ml, less than 30 ⁇ g/ml, less than 20 ⁇ g/ml, less than 15 ⁇ g/ml, less than 10 ⁇ g/ml, less than 5 ⁇ g/ml, less than 1 ⁇ g/ml, less than 0.1 ⁇ g/ml, less than 0.01 ⁇ g/ml, less than 0.001 ⁇ g/ml or less than 0.0001 ⁇ g/ml.
- the neutralizing capability of anti-MERS-S antibodies is measured in a virus-like particle (VLP) neutralization assay (Tang et al. (2012) PNAS 111(19):E2018-E2026).
- VLP virus-like particle
- whether a test antibody competes with a reference antibody for binding to MERS-S is determined using an in vitro binding competition assay.
- a Flag-tagged S1 domain or a Flag-tagged S2 domain may be immobilized to an anti-Flag biosensor, the association of the reference antibody to the immobilized Flag-tagged S1 or S2 domain is then measured (e.g. using the Octet® RED96 system, ForteBio, Inc.) and then the degree of additional binding is assessed by exposing the immobilized Flag-tagged Si or S2 domain to the test antibody in the presence of the reference antibody.
- the anti-MERS heavy chain-only antibody recognizes MERS-CoV and one or more additional beta coronaviruses.
- the anti-MERS antibody recognizes: (i) MERS-CoV and mouse hepatitis virus (MI-1V), (ii) MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV), or (iii) MERS-CoV, MI-IV and SARS-CoV.
- a combination of anti-MERS antibodies targeting different domains and functions of the viral glycoprotein may be more protective against virus infection than single epitope mAb therapy.
- the presence of protective antibody epitopes in multiple spike domains suggests that multi-domain approaches of spike-based vaccines may provide a broader repertoire of immune responses compared to RBD-focused vaccine antigen and reduce the risk of viral antigenic escape.
- a combination of antibodies provides synergistic protective activity against MERS-CoV.
- the invention provides a composition comprising two, three, four, five, six, seven, eight, nine or ten of the anti-MERS antibodies disclosed herein.
- the invention provides a combination of anti-MERS-S 1 antibody and an anti-MERS-S2 antibody.
- the 7.7g6 and 1.6c7 antibodies bind to the S1 and S2 domains of MERS-S, respectively (see
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.
- an anti-MERS-S antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the 1E10 heavy chain-only antibody exhibits neutralising activity (see FIG. 31 ) and the 1.10f3 H2L2 antibody targets the sialic acid binding MERS S1 A domain (see FIG. 5A ) and inhibits Sia-binding activity. Accordingly, in some embodiments, the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the 1G3 heavy chain-only antibody exhibits neutralising activity (see FIG. 31 ) and the 1.10f3 H2L2 antibody targets the sialic acid binding MERS S lA domain (see FIG. 5A ) and inhibits Sia-binding activity. Accordingly, in some embodiments, the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the 1H5 heavy chain-only antibody exhibits neutralising activity (see FIG. 31 ) and the 1.10f3 H2L2 antibody targets the sialic acid binding MERS S lA domain (see FIG. 5A ) and inhibits Sia-binding activity. Accordingly, in some embodiments, the invention provides a combination comprising:
- an anti-MERS-S heavy chain-only antibody comprising complementarity determining regions (CDRs) with the sequences of:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- the 5F1 heavy chain-only antibody exhibits neutralising activity (see FIG. 31 ) and the 1.10f3 H2L2 antibody targets the sialic acid binding MERS S lA domain (see FIG. 5A ) and inhibits
- the invention provides a combination comprising:
- an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the invention provides a combination comprising:
- FIG. 2H shows that the 63c12 antibody recognizes spike proteins from OC43, MERS and SARS viruses.
- the invention provides an anti-MERS-S antibody that binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the invention further provides an anti-MERS-S antibody that binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the invention further provides an anti-MERS-S antibody that competes for binding to MERS-S with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the invention further provides an anti-MERS-S antibody comprising complementarity determining regions (CDRs) with:
- the antibody competes for binding to MERS-S with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.
- the other antibodies in FIG. 2C also recognize spike proteins from different Coronaviruses. Similar functional properties can be expected to be associated with the antibodies defined below which share structural and binding characteristics with the antibodies in FIG. 2C .
- the invention provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- a Coronavirus spike protein e.g. MERS-S
- the invention provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488.
- a Coronavirus spike protein e.g. MERS-S
- a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of SEQ ID NO: 436.
- the invention provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486 and a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486 and a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486.
- a Coronavirus spike protein e.g. MERS-S
- a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 488 and a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486 and a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 486 and a light chain variable region of the amino acid sequence of SEQ ID NO: 437.
- the invention provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499.
- a Coronavirus spike protein e.g. MERS-S
- a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the antibody comprises: (i) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and (ii) an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with:
- a Coronavirus spike protein e.g. MERS-S
- an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 499 and a light chain variable region of the amino acid sequence of SEQ ID NO: 438.
- the invention provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497 and a light chain variable region of the amino acid sequence of SEQ ID NO: 439.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody binds to the same epitope as a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with an antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497 and a light chain variable region of the amino acid sequence of SEQ ID NO: 439.
- a Coronavirus spike protein e.g. MERS-S
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody competes for binding to a Coronavirus spike protein (e.g. MERS-S) with a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497.
- a Coronavirus spike protein e.g. MERS-S
- a heavy chain-only antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497.
- the invention further provides an antibody that binds to a Coronavirus spike protein (e.g. MERS-S), wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
- the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a heavy chain variable region of the amino acid sequence of SEQ ID NO: 497.
- the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 439.
- the antibody comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a light chain variable region of the amino acid sequence of SEQ ID NO: 439.
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WO2022047176A2 (en) * | 2020-08-28 | 2022-03-03 | University Of Houston System | Single-chain coronavirus viral membrane protein complexes |
EP4211158A1 (en) * | 2020-09-14 | 2023-07-19 | Nanjing Vazyme Biotech Co., Ltd. | Neutralizing antibodies against sars-cov-2 |
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US20230391852A1 (en) * | 2020-10-26 | 2023-12-07 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting sars coronavirus spike protein and uses thereof |
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2020
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- 2020-02-20 EP EP20707586.2A patent/EP3927432A2/en active Pending
- 2020-02-20 CN CN202080029620.1A patent/CN113874394B/zh active Active
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CN113874394B (zh) | 2024-01-19 |
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EP3927432A2 (en) | 2021-12-29 |
WO2020169755A3 (en) | 2020-10-01 |
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